Using standard histologic, immunohistochemical, electron microscopic and serologic techniques we propose to study the following aspects of the cutaneous immunopathology in New Zealand (NZ) mice: (1) the relationship between subepidermal immunoglobulin (Ig) deposits and renal disease, serum antibody to native DNA and skin lesions; (2) the possibility of epidermal contribution of DNA to the subepidermal DNA:anti-DNA complexes; (3) the effect on subepidermal Ig accumulation of local factors that influence the rate of epidermal DNA release and of agents that are known to bind to DNA; and (4) the morphologic and immunopathologic features of the skin lesions in the New Zealand White (NZW) mice. In addition, evidence for the presence of DNA responsive T lymphocytes will be looked for in NZ mice using both in vitro and in vivo techniques. The results of these studies will be correlated with the presence or absence of antibody to DNA and skin lesions. Information derived from these studies should be directly applicable to patients suffering with systemic lupus erythematosus. Specifically, these investigations may shed light on the role of ultraviolet light in precipitating systemic flares of the disease. They may also provide data regarding the therapeutic effectiveness of various antiinflammatory or immunosuppressive agents. The studies may give important insight into the mechanism of in-situ formation of immune complexes which has been considered of pathogenetic importance in a variety of disease states. BIBLIOGRAPHIC REFERENCES: Hurd, ER, Gilliam, JN and Ziff, Morris: The differential effects of cyclophosphamide and 6-mercaptopurine on the renal disease and skin Ig deposits of NZB/NZW Fl hybrid mice. Agts & Acts 6:364, 1976. Gilliam, JN: The Cutaneous Signs of Lupus Erythematosus. Continuing Education for the Family Physician 6:34-40, 1977.